Bronchopulmonary Dysplasia: Executive Summary of a Workshop

Higgins RD, Jobe AH, Koso-Thomas M, Bancalari E, Viscardi RM, Hartert TV, Ryan RM, Kallapur SG, Steinhorn RH, Konduri GG, Davis SD, Thebaud B, Clyman RI, Collaco JM, Martin CR, Woods JC, Finer NN, Raju TNK. Bronchopulmonary Dysplasia: Executive Summary of a Workshop. J Pediatr. 2018 Jun;197:300-308. doi: 10.1016/j.jpeds.2018.01.043. Epub 2018 Mar 16. PMID: 29551318; PMCID: PMC5970962.

Despite significant advances in perinatal care, bronchopulmonary dysplasia (BPD) remains one of the most common, complex, and intriguing diseases in perinatal medicine. The pathogenesis of BPD remains to be elucidated fully. Defining this disease continues to be imprecise and varies across institutions, and evidence-based guidelines addressing management are lacking. To address these and other knowledge gaps, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) held a workshop on BPD in October 2016. Information presented at the workshop included an overview of BPD providing a definition, epidemiology, pathogenesis pathways, and the strengths and limitations of available management options. The expert panel also discussed a research agenda; the use of advanced technology including medications, respiratory support measures, modern imaging, and management for preventing and treating BPD; and the current approach to the follow-up of these infants. The workshop panel developed a proposal for an updated definition for BPD based on prior definitions and current care practices. This report provides a summary of the workshop proceedings.

BPD was first described in 1967 by Northway et al in an era when the mortality from respiratory distress syndrome (RDS) was >50%.1 Infants who were ventilated and survived the initial phase of RDS often recovered slowly from their pulmonary injury. Northway et al reported the stages of lung injury progression.1 The authors named the disorder, BPD, a chronic disease with a “prolonged healing phase” of RDS. Oxygen toxicity, positive pressure ventilation, and endotracheal intubation were all implicated as causative factors for the development of BPD. Later, injuries from mechanical ventilation (“ventilator-induced lung injury”) captured by the catch phrase—“pressure + volume + time”—was emphasized2,3 as causative factors for BPD. Initially, researchers included radiologic features and pathologic findings when available to define BPD. As the survival rate of RDS increased with more BPD survivors, a clinical definition for BPD was adopted as “those infants requiring supplemental oxygen on post-natal day 28.” As more immature infants survived, it was felt that day 28 oxygen use could be related to other factors (eg, prematurity) and in 1988, Shennan et al refined the definition to oxygen use at 36 weeks postmenstrual age (PMA).

In 2000, a workshop sponsored by the National Heart, Lung and Blood Institute proposed a more comprehensive definition for BPD to help identify varying severity and, thus, they categorized BPD as “none, mild, moderate or severe.”5 “No BPD” was defined as <28 days of supplemental oxygen. Mild BPD included infants who received oxygen or respiratory support for >28 days but were on room air at 36 weeks PMA. Infants with moderate BPD required supplemental oxygen, <30% fraction of inspired oxygen concentration, at 36 weeks PMA. Finally, severe BPD was classified as the use of >30% oxygen or positive pressure at 36 weeks PMA. After the National Heart, Lung and Blood Institute workshop, a further refinement in the definition included a physiologic challenge of supplemental oxygen withdrawal to test for oxygen need at 36 weeks PMA.6 Infants were classified as “Yes BPD” by the “Physiologic definition of BPD” if they had an oxygen saturation of <88% within 60 minutes of a “room air challenge test.” Subsequently, the saturation target was increased to <90%.7,8 More recently, the Canadian Neonatal Network evaluated the definitions of BPD that were commonly used for epidemiology and clinical trial outcomes for predictability of lung disease and neurodevelopmental injury at 18–21 months of age and found that oxygen and/or respiratory support at 40 weeks PMA best predicted ongoing respiratory morbidity at 18–24 months of age.9 A limitation of using this later time point is that many infants are discharged from the hospital before 40 weeks PMA. Further, changes in neonatal respiratory support clinical practices including the use of high-flow nasal cannula with room air (21% oxygen) or very low flow with 100% oxygen make many infants unclassifiable by current standard BPD definitions.10 An attempt to compare various BPD definitions is worthwhile to establish which ones can more precisely predict long-term outcomes in babies discharged from the initial hospital stay.

The relationship between the definitions of BPD used for trials—typically oxygen use at 36 weeks PMA—and longer term outcomes have been inconsistent. For instance, decreased forced expiratory flows measured at 6 and 18 months using infant lung function techniques have not been associated with BPD.11 However, others have demonstrated that airway obstruction assessed during infancy is worse in those with BPD compared with those without this diagnosis.12 Furthermore, recent studies that show BPD is predictive of respiratory outcomes during the first 1–2 years of life.13 BPD is currently believed to result from the of combination of developmental immaturity, injury, inflammation, repair, and healing. Updates and modifications to the definition of BPD are necessary, given the changes in the neonatal preterm patient population as well as neonatal intensive care unit (NICU) clinical practices over time.

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